Days Ahead of PDUFA Date Gattex Wins Approval in SBS

By Jennifer BoggsManaging Editor

It may have taken more than two decades, but NPS Pharmaceuticals Inc. is set to launch its first commercial product in the first quarter, following Friday's FDA approval of Gattex (teduglutide [rDNA origin]) as a long-term treatment for short bowel syndrome (SBS).

"We are ready," said Francois Nader, president and CEO. Specific launch plans and anticipated cost of Gattex, a recombinant analogue of glucagon-like peptide 2 (GLP-2), aren't available yet; the firm is planning a Jan. 2 call to discuss those details. But Nader said NPS is getting its 30-member sales team prepped and has initiated a support program called NPS Advantage to provide patient education and assistance.

"Patients have been waiting 40 years for a long-term treatment," he told BioWorld Today. Gattex's approval is the "result of finding an answer to an unmet medical need in a patient population that is highly debilitated."

An orphan indication, SBS is estimated to affect about 10,000 to 15,000 in the U.S. It is typically caused by extensive resection of the bowel. SBS patients are unable to absorb sufficient nutrients and fluids in their gastrointestinal tracts and usually end up relying on frequent parenteral nutrition and/or intravenous fluids (PN/I.V.). Those PN/I.V. infusions can occur five to seven nights per week for up to 10 to 12 hours at a time, with extreme cases requiring 24-hour PN/I.V.

Gattex works by targeting GLP-2 to enhance fluid and nutrient absorption. In Phase III testing, it produced significant reductions in PN/I.V. volume and infusion days per week, compared to pre-treatment baseline, with some patients actually able to achieve PN/I.V. independence. Initial results showed a benefit for 63 percent of patients, and that figure grew to more than 90 percent in the ongoing STEPS 2 extension trial. (See BioWorld Today, Feb. 1, 2011.)

As of early November, NPS said 1 out of 7 patients had achieved independence in STEPS 2. That study is set to complete early next year.

Gattex's approval, which came nine days ahead of the PDUFA date  the original Sept. 30 PDUFA date had been extended for three months to give reviewers additional time  also had been largely expected, given the favorable briefing documents released followed by the unanimous recommendation by the FDA's Gastrointestinal Drugs Advisory Committee in October. (See BioWorld Today, Oct. 17, 2012.)

"We presented to the FDA a very extensive" data package, particularly given the relatively small SBS patient population, Nader said. "We went the extra mile to develop [Gattex], and we were rewarded by a 12-0 vote [by the adcom] and now we've been rewarded by approval."

In late 2011 , news of adverse effects raised some eyebrows, and, unsurprisingly, led to the FDA's warning that Gattex might increase the risks for cancer and polyps in the intestine and intestinal blockage. NPS also had to put together a risk evaluation and mitigation strategy. But those additions had been expected and, overall, Nader said he was "quite pleased with the label."

Shares of NPS (NASDAQ:NPSP) gained 4 cents Friday to close at $9. 10, and the Bedminster, N.J.-based company's shares have gained 35 percent on the year.

Staying in Orphan Space for 'Foreseeable Future'

Gattex's approval also marks a big win for NPS. The company has had a hand in a number of approved products, receiving royalty streams from the likes of Amgen Inc.'s Sensipar/Mimpara (cinacalcet HCl), Nycomed's Preotact (recombinant parathyroid hormone 1-84 [rDNA origin] injection) and Janssen Pharmaceuticals' Nucynta (tapentadol). But Gattex is the first product it advanced to market on its own.

"It took us 26 years to have our first own product," Nader noted.

Part of the firm's recent success is its switch to an orphan disease strategy. Following the FDA's rejection in 2006 of osteoporosis drug Preos (recombinant parathyroid hormone), NPS' shares crashed, and many were left wondering whether there was a future for the firm. NPS rebounded, trimming its staff and redirecting its focus, to emerge a few years later with two orphan candidates in late-stage development. (See BioWorld Insight, Jan. 31, 2011.)

"We like the space," Nader acknowledged. "It's a space where there is unmet medical need," and NPS plans to continue working in orphan diseases for "the foreseeable future."

Beyond Gattex, NPS is working on a biologics license application (BLA) filing for a second orphan product: Natpara (NPSP558), a bioengineered replica of human parathyroid hormone, in adults with hypoparathyroidism. Though the firm initially hoped to submit the Natpara BLA in 2012, the FDA requested changes to the instructions for the device used to deliver Natpara, and NPS said it plans to file for approval in the middle of 2013.

The company, which ended the third quarter with about $119 million on its balance sheet, has sufficient funding to get both Gattex and Natpara to market, Nader said, though NPS will remain opportunistic about raising money.

"We could do it, but we certainly don't have to do it," he added.

The company has taken advantage of its royalty streams from partnered programs, which brought in total revenues of $27 million in the third quarter. And last year, NPS inked a deal with Thousand Oaks, Calif.-based Amgen to get a $145 million advance on Sensipar royalties to pad its balance sheet. (See BioWorld Today, Aug. 17, 2011.)

NPS also is entitled to double-digit royalties from net sales of Gattex outside the U.S.

Earlier this year, partner Takeda Pharmaceutical Co. Ltd. (which gained rights to the drug via its buyout of Nycomed A/S), gained approval of the drug in Europe, where it is branded Revestive.